Patient-Informed Value Elements in Cost-Effectiveness Analyses of Major Depressive Disorder Treatment: A Literature Review and Synthesis.

OBJECTIVES: Prior work identified six key value elements (attributes of treatment and desired outcomes) for individuals living with major depressive disorder (MDD) in managing their condition: Mode of Treatment, Time to Treatment Helpfulness, MDD Relief, Quality of Work, Interaction with Others, and Affordability. The objective of our study was to identify whether previous cost-effectiveness analyses (CEAs) for MDD treatment addressed any of these value elements. A secondary objective was to identify whether any study engaged patients, family members, and caregivers in the model development process. METHODS: We conducted a systematic literature review to identify published model-based CEAs. We compared the elements of the published studies to the MDD patient value elements elicited in prior work to identify gaps and areas for future research. RESULTS: Of 86 published CEAs, we found that seven included patient out-of-pocket costs, and 32 included measures of productivity, which were both priorities for individuals with MDD. We found that only two studies elicited measures from patients for their model and two studies engaged patients in the modeling process. CONCLUSIONS: Published CEA models for MDD treatment do not regularly include value elements that are a priority for this patient population, nor do they include patients in their modeling process. Flexible models that can accommodate elements consistent with patient experience are needed and a multi-stakeholder engagement approach would help accomplish this.

Real-world treatment modalities, health care resource utilization, and costs among commercially insured patients with newly diagnosed major depressive disorder in the United States.

BACKGROUND: In the United States, major depressive disorder (MDD) is one of the most prevalent mental health disorders. Treatment guidelines for MDD recommend pharmacologic and nonpharmacologic therapies tailored to the patient's disease severity, level of function, and comorbid health conditions. While previous studies examined real-world pharmacologic treatment patterns and costs among patients with MDD, few have examined the use of nonpharmacologic treatments and their association with health care resource utilization (HCRU) and cost. OBJECTIVE: To describe prevalence and associations between patient/provider characteristics and treatment modality and characterize HCRU and cost by treatment modality for patients with newly diagnosed MDD. METHODS: Commercially insured US patients, aged 18-62 years with newly diagnosed MDD between January 1, 2017, and September 30, 2019, were retrospectively identified from the Healthcare Integrated Research Database. Eligible patients were continuously enrolled in the health plan for 1 year before and 2 years after the first MDD diagnosis (index date). Those with co-occurring schizophrenia, bipolar disorder, postpartum depression, substance use disorder, and any prior MDD treatments were excluded. Treatment modalities assessed in the 2-year post-index period included antidepressant only (Rx-only), nonpharmacologic only (non-Rx-only), both antidepressant and nonpharmacologic (combination), and no treatment. HCRU and costs were assessed in the 2-year post-index period by treatment modality. Regression models identified associations between patient/provider characteristics and treatment modality, and the relationship between treatment modality and MDD severity changes. RESULTS: In total, 12,657 patients were included (mean age: 36 years; 60% female). During follow-up, 34% of patients received Rx-only, 25% received non-Rx-only, 28% received combination, and 13% received no treatment. MDD severity at diagnosis (26% mild, 54% moderate, 20% severe) was available for 51% of patients. Post-index inpatient hospitalizations were 11% for those with Rx-only, 10% for non-Rx-only, 16% for combination, and 29% for no treatment, whereas all-cause mean monthly total costs were $792, $633, $786, and $1,292, respectively. In multinomial logistic regression, age, sex, geographic region and urbanicity of patient residence, socioeconomic status, diagnosing provider specialty, and initial diagnosis location were significantly associated (P < 0.05) with treatment modality. In multivariable logistic regression, recipients of Rx-only (odds ratio = 2.03, P < 0.01) or combination (odds ratio = 3.26, P < 0.01) had higher odds of improving MDD severity than patients who received no treatment. CONCLUSIONS: In this real-world sample of commercially insured patients, we observed variations in outcomes by treatment modality and an association between treatment modality and disease severity. Further research is needed to explore the underlying causal relationships between treatment modality and patient outcomes. Study Registration: https://doi.org/10.17605/OSF.IO/YQ6B3 DISCLOSURES: Dr Grabner is an employee of Carelon Research, which received funding from the Innovation and Value Initiative for the conduct of the study on which this manuscript is based. Ms Pizzicato and Mr Yang were employees of Carelon Research at the time the study was conducted. Dr Grabner is a shareholder of Elevance Health. Drs Xie and Chapman are employees of the Innovation and Value Initiative.

Treatment goals for rheumatoid arthritis: patient engagement and goal collection.

Aim: We developed the Patient-Engaged Health Technology Assessment strategy for survey-based goal collection from patients to yield patient-important outcomes suitable for use in multi-criteria decision analysis. Methods: Rheumatoid arthritis patients were recruited from online patient networks for proof-of-concept testing of goal collection and prioritization using a survey. A Project Steering Committee and Expert Panel rated the feasibility of scaling to larger samples. Results: Survey respondents (n = 47) completed the goal collection exercise. Finding effective treatments was rated by respondents as the most important goal, and reducing stiffness was rated as the least important. Feedback from our steering committee and expert panel support the approach's feasibility for goal identification and ranking. Conclusion: Goals relevant for treatment evaluation can be identified and rated for importance by patients to permit wide input from patients with lived experience of disease.

Cost-Effectiveness of Nadofaragene Firadenovec and Pembrolizumab in Bacillus Calmette-Guérin Immunotherapy Unresponsive Non-Muscle Invasive Bladder Cancer.

OBJECTIVES: Nadofaragene firadenovec is a gene therapy for bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) undergoing Food and Drug Administration review. Pembrolizumab is approved for treating patients with BCG-unresponsive NMIBC with carcinoma in situ (CIS). We evaluated the cost-effectiveness of these treatments compared with a hypothetical therapeutic alternative, at a willingness-to-pay threshold of $150 000 per quality-adjusted life-year (QALY) gained, in CIS and non-CIS BCG-unresponsive NMIBC populations. METHODS: We developed a Markov cohort simulation model with a 3-month cycle length and lifetime horizon to estimate the total costs, QALYs, and cost per additional QALY from the health sector perspective. Clinical inputs were informed by results of single-arm clinical trials evaluating the treatments, and systematic literature reviews were conducted to obtain other model inputs. Sensitivity analyses were conducted to assess uncertainty in model results. RESULTS: Nadofaragene firadenovec, at a placeholder price 10% higher than the price of pembrolizumab, had an incremental cost-effectiveness ratio of $263 000 and $145 000 per QALY gained in CIS and non-CIS populations, respectively. Pembrolizumab had an incremental cost-effectiveness ratio of $168 000 per QALY gained for CIS. A 5.4% reduction in pembrolizumab's price would make it cost-effective. The model was sensitive to many inputs, especially to the probabilities of disease progression, initial treatment response and durability, and drug price. CONCLUSIONS: The cost-effectiveness of nadofaragene firadenovec will depend upon its price. Pembrolizumab, although not cost-effective in our base-case analysis, is an important alternative in this population with an unmet medical need. Comparative trials of these treatments are warranted to better estimate cost-effectiveness.

Preferences for Treatments for Major Depressive Disorder: Formative Qualitative Research Using the Patient Experience.

OBJECTIVES: The goals of this formative research are to elicit attributes of treatment and desired outcomes that are important to individuals with major depressive disorder (MDD), to develop a stated preference instrument, and to pre-test the instrument. METHODS: A three-phase survey study design elicited the patient's journey with MDD to design and pre-test the discrete choice experiment (DCE) instrument. Participants were 20 adults aged ≥ 18 with MDD who did not also have bipolar disorder or post-partum depression. We engaged patient advocates and a multi-disciplinary stakeholder advisory group to select and refine attributes for inclusion in a DCE instrument. The DCE was incorporated into a survey that also collected depression treatment and management and sociodemographic characteristics. The DCE was pre-tested with ten adults with MDD. RESULTS: Six attributes were included in the DCE: mode of treatment (medicine only, psychotherapy only, all modalities including brain stimulation), time to treatment effect (6, 9, 12 weeks), days of hopefulness (2, 4, 6 days/week), effect on productivity (40%, 60%, 90% increase), relations with others (strained, improved, no impact), and out-of-pocket costs ($30, $60, $90/month). The DCE test led to the refinement of mode of treatment (medicine, medicine and psychotherapy, and all modalities); time to treatment effect (4, 6, 9 weeks); monthly out-of-pocket costs ($30, $90, $270). CONCLUSIONS: MDD treatment preferences revealed trade-offs among mode of treatment, time to treatment effect, functional outcomes, and cost. The findings demonstrate the potential for meaningfully incorporating the patient experience in preference measures.

The Cost-Effectiveness of Belimumab and Voclosporin for Patients with Lupus Nephritis in the United States.

BACKGROUND AND OBJECTIVES: Despite existing therapies, people with lupus nephritis progress to kidney failure and have reduced life expectancy. Belimumab and voclosporin are two new disease-modifying therapies recently approved for the treatment of lupus nephritis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A de novo economic model was developed to estimate the cost-effectiveness of these therapies, including the following health states: "complete response," "partial response," and "active disease" defined by eGFR and proteinuria changes, kidney failure, and death. Short-term data and mean cohort characteristics were sourced from pivotal clinical trials of belimumab (the Belimumab International Study in Lupus Nephritis) and voclosporin (the Aurinia Urinary Protection Reduction Active-Lupus with Voclosporin trial and Aurinia Renal Response in Active Lupus With Voclosporin). Risk of mortality and kidney failure were on the basis of survival modeling using published Kaplan-Meier data. Each drug was compared with the standard of care as represented by the comparator arm in its respective pivotal trial(s) using US health care sector perspective, with a societal perspective also explored. RESULTS: In the health care perspective probabilistic analysis, the incremental cost-effectiveness ratio for belimumab compared with its control arm was estimated to be approximately $95,000 per quality-adjusted life year. The corresponding incremental ratio for voclosporin compared with its control arm was approximately $150,000 per quality-adjusted life year. Compared with their respective standard care arms, the probabilities of belimumab and voclosporin being cost effective at a threshold of $150,000 per quality-adjusted life year were 69% and 49%, respectively. Cost-effectiveness was dependent on assumptions made regarding survival in response states, costs and utilities in active disease, and the utilities in response states. In the analysis from a societal perspective, the incremental ratio for belimumab was estimated to be approximately $66,000 per quality-adjusted life year, and the incremental ratio for voclosporin was estimated to be approximately $133,000 per quality-adjusted life year. CONCLUSIONS: Compared with their respective standard care arms, belimumab but not voclosporin met willingness-to-pay thresholds of $100,000 per quality-adjusted life year. Despite potential clinical superiority in the informing trials, there remains high uncertainty around the cost-effectiveness of voclosporin.

Does Cost-Effectiveness Analysis Overvalue Potential Cures? Exploring Alternative Methods for Applying a "Shared Savings" Approach to Cost Offsets.

OBJECTIVES: To evaluate alternative methods to calculate and/or attribute economic surplus in the cost-effectiveness analysis of single or short-term therapies. METHODS: We performed a systematic literature review of articles describing alternative methods for cost-effectiveness analysis of potentially curative therapies whose assessment using traditional methods may suggest unaffordable valuations owing to the magnitude of estimated long-term quality-adjusted life-year (QALY) gains or cost offsets. Through internal deliberation and discussion with staff at the Health Technology Assessment bodies in England and Canada, we developed the following 3 alternative methods for further evaluation: (1) capping annual costs in the comparator arm at $150 000 per year; (2) "sharing" the economic surplus with the health sector by apportioning only 50% of cost offsets or 50% of cost offsets and QALY gains to the value of the therapy; and (3) crediting the therapy with only 12 years of the average annual cost offsets or cost offsets and QALY gains over the lifetime horizon. The impact of each alternative method was evaluated by applying it in an economic model of 3 hypothetical condition-treatment scenarios meant to reflect a diversity of chronicity and background healthcare costs. RESULTS: The alternative with greatest impact on threshold price for the fatal pediatric condition spinal muscular atrophy type 1 was the 12-year cutoff scenario. For a hypothetical one-time treatment for hemophilia A, capping cost offsets at $150 000 per year had the greatest impact. For chimeric antigen receptor T-cell treatment of non-Hodgkin's lymphoma, capping cost offsets or using 12-year threshold had little impact, whereas 50% sharing of surplus including QALY gains and cost offsets greatly reduced threshold pricing. CONCLUSIONS: Health Technology Assessment bodies and policy makers will wrestle with how to evaluate single or short-term potentially curative therapies and establish pricing and payment mechanisms to ensure sustainability. Scenario analyses using alternative methods for calculating and apportioning economic surplus can provide starkly different assessment results. These methods may stimulate important societal dialogue on fair pricing for these novel treatments.

Developing a Framework for the Health Technology Assessment of Histology-independent Precision Oncology Therapies.

The arrival of precision oncology is challenging the evidence standards under which technologies are evaluated for regulatory approval as well as for health technology assessment (HTA) purposes. Several key concepts are discussed to highlight the source of the challenges in evaluating these products, particularly those impacting the HTA of histology-independent therapies. These include the basket trial design, high uncertainty in (potentially substantial) benefits for histology-independent therapies, and the inability to identify and quantify benefits of standard of care in daily practice when the biomarker is not currently used in practice. There is little precedent for a technology with the unique mixture of challenges for HTA of histology-independent therapies and they will be evaluated using standard HTA, as there currently is no evidence suggesting the standard HTA framework is not appropriate. A number of questions proposed to help guide HTA bodies when assessing the appropriateness of local processes to optimally evaluate histology-independent therapies. Pragmatic solutions are further proposed to decrease uncertainty in the benefits of histology independent therapies as well as fill gaps in comparative evidence. The proposed solutions ensure a consistent and streamlined approach to evaluation across histology-independent products, although with varying strengths and limitations. Alongside these solutions, sponsors should engage early with HTA bodies/payers and regulatory agencies through parallel/joint scientific advice to facilitate the integration of both regulatory and HTA perspectives into one clinical development programme, potentially reconciling evidence requirements.

Cost-effectiveness of oral semaglutide added to current antihyperglycemic treatment for type 2 diabetes.

BACKGROUND: Oral semaglutide is the first oral formulation of a glucagon-like peptide 1 (GLP-1) receptor agonist to be approved in the United States for glycemic control in people with type 2 diabetes mellitus (T2DM). While oral semaglutide is not indicated for reduction of cardiovascular event risk, its label does include evidence of no increase in cardiovascular risk in people who received oral semaglutide. OBJECTIVE: To estimate the incremental value of oral semaglutide added to existing antihyperglycemic treatment for people with T2DM with additional risk for cardiovascular disease. METHODS: We estimated the lifetime cost-effectiveness of oral semaglutide added to current antihyperglycemic treatment for T2DM using a microsimulation model based primarily on the UK Prospective Diabetes Study (UKPDS) Outcomes Model 2 (OM2) equations. Oral semaglutide added to current antihyperglycemic treatment was separately compared with (a) ongoing background antihyperglycemic treatment, (b) sitagliptin, (c) empagliflozin, and (d) liraglutide. Comparators sitagliptin, empagliflozin, and liraglutide were added to ongoing antihyperglycemic treatment. We applied hazard ratios derived from a network meta-analysis for cardiovascular and renal outcomes to the UKPDS OM2 estimated baseline rates. Health state utilities and costs were derived from the published literature. We estimated total costs, life-years (LYs), quality-adjusted life-years (QALYs), clinical events, and cost per major adverse cardiovascular event (MACE) avoided, over a lifetime time horizon using discount rates of 3% for costs and outcomes. RESULTS: The lifetime total cost for people treated with oral semaglutide was $311,300, with costs for the other comparators ranging from $262,800 (background treatment alone) to $287,800 (liraglutide). Oral semaglutide resulted in the fewest MACE, including the fewest cardiovascular deaths. Among the 5 modeled treatment strategies, oral semaglutide had the highest LYs gained (8.43 vs. 7.76 [background treatment alone] to 8.29 [empagliflozin and liraglutide]) and the highest QALYs gained (4.11 vs. 3.70 [background treatment alone] to 4.03 [empagliflozin]). Oral semaglutide would likely be considered cost-effective compared with liraglutide (incremental cost-effectiveness ratio [ICER] = $40,100), and moderately cost-effective versus background treatment alone ([ICER] = $117,500/QALY) and sitagliptin (ICER = $145,200/QALY). The ICER for oral semaglutide compared with empagliflozin was approximately $458,400 per QALY. CONCLUSIONS: As modeled, oral semaglutide as an add-on therapy to background antihyperglycemic treatment produced incremental benefits in MACE avoided, along with greater QALYs compared with background antihyperglycemic treatment alone. Oral semaglutide use resulted in better outcomes than background treatment alone or sitagliptin, and similar outcomes to liraglutide or empagliflozin with overlapping 95% confidence ranges for QALYs. Oral semaglutide was estimated to be cost-effective compared with liraglutide and to have incremental cost-effectiveness ratios between $100,000 and $150,000 per QALY versus sitagliptin and background therapy alone, but it did not meet these thresholds compared with empagliflozin. DISCLOSURES: Funding for this study was provided by the Institute for Clinical and Economic Review, an independent organization that evaluates the evidence on the value of health care interventions. ICER reports grants from Laura and John Arnold Foundation, California Health Care Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan. ICER's annual policy summit is supported by dues from AbbVie, Aetna, America's Health Insurance Plans, Anthem, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Cambia Health Services, CVS, Editas, Evolve Pharmacy, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, Health Partners, Humana, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, uniQure, and United Healthcare. Rind, Fazioli, Chapman, and Pearson are employed by ICER. Guzauskas and Hansen have nothing to disclose. Study results were presented at the New England Comparative Effectiveness Public Advisory Council (New England CEPAC), November 14, 2019, at Brown University, Providence, RI.

Cost-Effectiveness of Ivacaftor Therapy for Treatment of Cystic Fibrosis Patients With the G551D Gating Mutation.

OBJECTIVES: Cystic fibrosis (CF) is a rare genetic disease with no cure. Until recently, treatment has targeted symptoms of the disease and not the disease-causing genetic defect. Ivacaftor is included in a new class of breakthrough drugs targeting the genetic defects of CF. We sought to estimate the long-term cost-effectiveness of ivacaftor from a US payer perspective. METHODS: We developed an individual-level microsimulation model that followed a cohort of heterogeneous US CF patients over a lifetime. The primary outcome of interest was quality-adjusted life years (QALYs). We also compared unadjusted life years, count of acute pulmonary exacerbations, and count of lung transplants over a lifetime between patients treated with ivacaftor plus best supportive care and patients treated with best supportive care alone. We conducted one-way and probabilistic sensitivity analyses to test the impact of various model inputs and uncertainties. RESULTS: We found a substantial increase in QALYs, life years, and treatment costs over a lifetime for patients treated with ivacaftor plus best supportive care versus best supportive care alone. Discounted results for ivacaftor were 22.92 QALYs and $8 797 840 in total lifetime costs compared to 16.12 QALYs and $2 336 366 lifetime costs for best supportive care alone. The incremental cost-effectiveness ratios (ICERs) were $950 217 per QALY. Results from the probabilistic sensitivity analysis indicated a 0% chance that ivacaftor was cost-effective at a willingness-to-pay (WTP) threshold of $500 000 per QALY. CONCLUSIONS: Treatment with ivacaftor plus best supportive care versus best supportive care alone is not cost-effective at or near commonly accepted WTP thresholds.

Cost effectiveness of nusinersen for patients with infantile-onset spinal muscular atrophy in US.

BACKGROUND: Patients with infantile-onset spinal muscular atrophy (SMA), a rare, genetic neuromuscular disease, do not achieve key motor function milestones (e.g., sitting) and have short life expectancy in the absence of treatment. Nusinersen is a disease-modifying therapy for patients with SMA. OBJECTIVE: The aim of this study was to estimate the cost-effectiveness of nusinersen compared to best supportive care (BSC) in patients diagnosed with infantile-onset SMA in the US. METHODS: A de novo economic model was developed with the following health states: "permanent ventilation", "not sitting", "sitting", "walking", and "death". Short-term data were sourced from the pivotal clinical trials and studies of nusinersen (ENDEAR and SHINE). Motor function milestones achieved at the end of follow-up in the clinical trials were assumed to be sustained until death. Mortality risks were based on survival modelling of relevant published Kaplan-Meier data. Costs, life years (LYs), and quality-adjusted life years (QALYs) were discounted at 3% per annum, and the analyses were performed from a US health care sector perspective. Scenario analyses and sensitivity analyses were conducted to assess the robustness of the results to key parameters. RESULTS: In our base-case analysis, nusinersen treatment achieves greater QALYs and more LYs (3.24 and 7.64, respectively) compared with BSC (0.46 QALYs and 2.40 LYs, respectively), resulting in an incremental cost per QALY gained of approximately $1,112,000 and an incremental cost per LY gained of $590,000 for nusinersen compared to BSC. The incremental cost effectiveness ratios did not fall below $990,000 per QALY gained in scenario and sensitivity analyses. Results were most sensitive to the length of survival, background health care costs, and utility in the "not sitting" and "sitting" health states. CONCLUSIONS: The estimated incremental cost-effectiveness of nusinersen from a US health care sector perspective exceeded traditional cost-effectiveness thresholds. Cost-effectiveness was dependent on assumptions made regarding survival, costs, utilities, and whether the motor function milestones were sustained over lifetime. Given the relatively short-term effectiveness data available for the treatment, a registry to collect long-term data of infantile-onset SMA patients is recommended.

Achieving Appropriate Model Transparency: Challenges and Potential Solutions for Making Value-Based Decisions in the United States.

Transparency in decision modeling remains a topic of rigorous debate among healthcare stakeholders, given tensions between the potential benefits of external access during model development and the need to protect intellectual property and reward research investments. Strategies to increase decision model transparency by allowing direct external access to a model's structure, source code, and data can take on many forms but are bounded between the status quo and free publicly available open-source models. Importantly, some level of transparency already exists in terms of methods and other technical specifications for published models. The purpose of this paper is to delineate pertinent issues surrounding efforts to increase transparency via direct access to models and to offer key considerations for the field of health economics and outcomes research moving forward from a US academic perspective. Given the current environment faced by modelers in academic settings, expected benefits and challenges of allowing direct model access are discussed. The paper also includes suggestions for pathways toward increased transparency as well as an illustrative real-world example used in work with the Institute for Clinical and Economic Review to support assessments of the value of new health interventions. Potential options to increase transparency via direct model access during model development include adequate funding to support the additional effort required and mechanisms to maintain security of the underlying intellectual property. Ultimately, the appropriate level of transparency requires balancing the interests of several groups but, if done right, has the potential to improve models and better integrate them into healthcare priority setting and decision making in the US context.

United States Valuation of EQ-5D-5L Health States Using an International Protocol.

OBJECTIVE: To derive a US-based value set for the EQ-5D-5L questionnaire using an international, standardized protocol developed by the EuroQol Group. METHODS: Respondents from the US adult population were quota-sampled on the basis of age, sex, ethnicity, and race. Trained interviewers guided participants in completing composite time trade-off (cTTO) and discrete choice experiment (DCE) tasks using the EuroQol Valuation Technology software and routine quality control measures. Data were modeled using a Tobit model for cTTO data, a mixed logit model for DCE data, and a hybrid model that combined cTTO and DCE data. Model performance was compared on the basis of logical ordering of coefficients, statistical significance, parsimony, and theoretical considerations. RESULTS: Of 1134 respondents, 1062, 1099, and 1102 respondents provided useable cTTO, DCE, and cTTO or DCE responses, respectively, on the basis of quality control criteria and interviewer judgment. Respondent demographic characteristics and health status were similar to the 2015 US Census. The Tobit model was selected as the preferred model to generate the value set. Values ranged from -0.573 (55 555) to 1 (11 111), with 20% of all predicted health states scores less than 0 (ie, worse than dead). CONCLUSIONS: A societal value set for the EQ-5D-5L was developed that can be used for economic evaluations and decision making in US health systems. The internationally established, standardized protocol used to develop this US-based value set was recommended by the EuroQol Group and can facilitate cross-country comparisons.

New Cost-Effectiveness Methods to Determine Value-Based Prices for Potential Cures: What Are the Options?

Evaluating different approaches to assessing the clinical effectiveness and value of potential cures will be essential to arm the policymaker, payer, and manufacturer communities with a platform that can reward innovation while supporting a sustainable health insurance system. Potential cures will accentuate concerns about substantial uncertainty in long-term outcomes. They will also focus attention on whether broader elements of value need to be incorporated and whether specific social values have a special place in evaluations of potential cures. In addition, the large magnitudes of potential health gain and cost offsets may require new methods before translation into value-based price recommendations. This article analyzes the challenges and presents several options to modify the conduct and presentation of cost-effectiveness analyses to ensure they provide policy-relevant assessments of the value of potential cures.

Can We Develop Sustainable and Sharable Cost-Effectiveness Models for Value Assessment in the U.S. Health Care System?

There is currently a movement to make economic models more transparent, with some arguing for completely open-source models. However, increasing model transparency raises several logistical challenges, including ownership and funding. This article outlines recent experience and approaches to some of the logistical hurdles that must be overcome in pursuit of more transparent economic models. The Institute for Clinical and Economic Review (ICER) has recently completed a pilot transparency initiative that made drafts of executable economic models available to involved drug manufacturers during the review process. By directly viewing and interacting with models' structures, inputs, key assumptions, and results, stakeholders were better equipped to provide valuable feedback as part of the health technology assessments. This experience, along with feedback received from the modeling collaborators and relevant manufacturers during this pilot, have helped determine ICER's approach to sharing economic models associated with ongoing and future evidence reviews. This process has been expanded to all assessments going forward, making it the standard approach to model transparency. DISCLOSURES: No outside funding supported the writing of this article. Both authors are employees of the Institute for Clinical and Economic Review (ICER), which is an an independent organization that evaluates the evidence on the value of health care interventions. ICER receives grant funding from the California Healthcare Foundation, Laura and John Arnold Foundation, and New England States Consortium Systems Organization. ICER's annual policy summit is supported by dues from Aetna, AHIP, Allergan, Alnylam, Anthem, AstraZeneca, Biogen, Blue Shield of California, Cambia Health Services, CVS Caremark, Editas, Express Scripts, Genentech, GlaxoSmithKline, Harvard Pilgrim Health Care, Health Care Service Corporation, Health Partners, Johnson & Johnson, Kaiser Permanente, LEO, Mallinckrodt, Merck, National Pharmaceutical Council, Novartis, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, and United Healthcare.

Impact of Abuse Deterrent Formulations of Opioids in Patients With Chronic Pain in the United States: A Cost-Effectiveness Model.

OBJECTIVE: Opioid abuse is a significant public health problem in the United States. We evaluate the clinical effectiveness and economic impact of abuse-deterrent formulations (ADF) of opioids relative to non-ADF opioids in preventing abuse. METHODS: We developed a cost-effectiveness model simulating 2 cohorts of 100 000 noncancer, chronic-pain patients newly prescribed either ADF or non-ADF extended-release (ER) opioids and followed them over 5 years, tracking new events of opioid abuse and opioid-related overdose deaths in addition to tracking 5-year cumulative costs of therapeutic use and abuse of ADF and non-ADF opioids. Patients in each cohort entered the model for therapeutic opioid use from where they could continue in that pathway, discontinue opioid use, or abuse opioids or die of opioid overdose-related or unrelated causes. In addition, one-way sensitivity and scenario analysis were conducted. RESULTS: Over a 5-year time period, using ADF opioids prevented an additional 2300 new cases of opioid abuse at an additional cost of approximately $535 million to the healthcare sector. Threshold analyses showed that a 40% decrease in ADF opioid costs was required to attain cost neutrality between the 2 cohorts, whereas a 100% effectiveness in abuse reduction still did not result in cost neutrality. A 43% decrease in diversion with ADFs relative to non-ADFs was required to attain cost neutrality. Including a societal perspective produced results directionally similar to the base-case analysis findings. CONCLUSION: ADF opioids have the potential to prevent new cases of opioid abuse, but at substantially higher costs to the health system.

Long-term Survival and Cost-effectiveness Associated With Axicabtagene Ciloleucel vs Chemotherapy for Treatment of B-Cell Lymphoma.

Importance: Axicabtagene ciloleucel, a chimeric antigen receptor T-cell therapy, represents a new and potentially curative treatment option for B-cell lymphoma. It is expected to have long-term survival benefits; however, long-term survival data are limited. Objective: To estimate the long-term survival and cost-effectiveness of axicabtagene ciloleucel for treatment of relapsed or refractory B-cell lymphoma. Design, Setting, and Participants: Economic evaluation study using a survival analysis that digitized and extrapolated survival curves published in the ZUMA-1 trial (Safety and Efficacy of KTE-C19 in Adults With Refractory Aggressive Non-Hodgkin Lymphoma), which enrolled patients between November 2015 and September 2016 and had a maximum follow-up of 24 months. Five different survival models (standard parametric, flexible parametric, 2 mixture cure models, and a flexible parametric mixture model) were used to extrapolate the survival curves to a lifetime horizon from January through June 2018. A cost-effectiveness analysis, from both a trial-based and lifetime horizon, was also conducted to inform the value of this novel therapy. The model was based on data from 111 patients with B-cell lymphoma who were enrolled in the ZUMA-1 trial. Interventions: One-time administration of axicabtagene ciloleucel compared with chemotherapy. Main Outcomes and Measures: Undiscounted and discounted life-years (LYs) and quality-adjusted life-years (QALYs), total costs, and incremental costs per LY and QALY gained. Results: The modeled cohort of 111 patients started at 58 years of age. At the end of the trial, treatment with axicabtagene ciloleucel resulted in 0.48 more LYs and 0.34 more QALYs than chemotherapy, producing a cost-effectiveness estimate of $896 600 per QALY for public payers and $1 615 000 per QALY for commercial payers. Extrapolated long-term survival for patients treated with axicabtagene ciloleucel ranged from 2.83 to 9.19 discounted LYs and from 2.07 to 7.62 discounted QALYs. Incrementally, treatment with axicabtagene ciloleucel was associated with 1.89 to 5.82 discounted LYs and 1.52 to 4.90 discounted QALYs vs chemotherapy. With the use of these incremental estimates of survival, cost-effectiveness estimates ranged from $82 400 to $230 900 per QALY gained for public payers and from $100 400 to $289 000 per QALY gained for commercial payers. Conclusions and Relevance: Treatment with axicabtagene ciloleucel appears to be associated with incremental gains in survival over chemotherapy. The range in projected long-term survival was wide and reflected uncertainty owing to limited follow-up data. Cost-effectiveness is associated with long-term survival, with further evidence needed to reduce uncertainty.